Lesioning of deep prepiriform cortex protects against ischemic neuronal necrosis by attenuating extracellular glutamate concentrations

Abstract

An area of the deep prepiriform cortex is a controlling site for limbic seizures. Focal pharmacologic blockade of NMDA receptors in the deep prepiriform cortex protects against hippocampal cell injury during limbic seizures induced by intravenous kainate and during the excitotoxicity of global ischemia. In the current study, the deep prepiriform cortex was lesioned bilaterally by microinjection of kainate, 3 days before 10 min of global ischemia induced by four-vessel occlusion. Extracellular glutamate concentrations in the hippocampus were measured before, during, and after global ischemia by using in vivo microdialysis technique. Surviving hippocampal neurons were counted 7 days after ischemia. Lesioned animals showed significantly greater numbers of surviving neurons and significantly lower ischemia-induced elevations of extracellular glutamate concentrations than non-lesioned animals. During seizures induced from the deep prepiriform cortex, the immediate early gene cox-2 is expressed in the hippocampus. These results indicate that deep prepiriform cortex can be a modulatory site for ischemic hippocampal injury.